Much of the communication carried out by neurons in the central nervous system is mediated by specific proteins, such as neurotransmitter-gated ion channels localized in specific regions of a nerve cell. Elucidating how the structure of such neurotransmitter receptors relates to their function and how they are specifically localized is important in understanding the basis for genetic and pathological variations in receptor functions and for designing therapeutic strategies. Molecular approaches for identifying nucleotide sequences that encode neurotransmitter receptors from the brain have demonstrated a host of variants of several neurotransmitter receptors whose functions have not been clearly delineated. In contrast, much is known about the types of neurotransmitter receptors and the locations of neurons that bear various receptors in the nervous system of the marine mollusk, Aplysia californica. The Polymerase chain Reaction (PCR) amplification of specific stretches of Aplysia nucleic acids is being used to produce probes for various neurotransmitter receptors in the Aplysia nervous system. These and longer probes are being used for in-situ hybridization studies that will be used to identify the type of receptor encoded by the nucleotide probes. Initial observations that probes to neuronal actin hybridize to nerve fibers long distances from the cell body are being pursued on sections of Aplysia ganglia and in cultured neurons to determine the extent of actin mRNA translocation. Studies on cultured neurons that separate the growing neurites from the cell body will permit labeling of the neurites separately from the cell bodies to determine if actin is synthesized in the isolated neurites. The approaches developed for studying the translocation and disposition of actin will be used to determine whether the mRNA of a specific neuropeptide, FMRFamide, is also translocated and translated. In situ hybridization using PCR will be developed to amplify mRNA that may be present in minute quantities in neurites and in neuronal terminals. If local protein synthesis occurs in specific regions of neurons, then aberrant translocation of mRNA may be the basis for certain neurodegenerative diseases and altered targeting of important neuronal constituents.